CN107098894A - The heterocyclic radical propylene hydrazide derivative of 2 cyano group of N (2 thienyl) methylene 3 and its application - Google Patents
The heterocyclic radical propylene hydrazide derivative of 2 cyano group of N (2 thienyl) methylene 3 and its application Download PDFInfo
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- CN107098894A CN107098894A CN201710487689.9A CN201710487689A CN107098894A CN 107098894 A CN107098894 A CN 107098894A CN 201710487689 A CN201710487689 A CN 201710487689A CN 107098894 A CN107098894 A CN 107098894A
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- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 title abstract description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 title abstract description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 title abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 16
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 241000144210 Culex pipiens pallens Species 0.000 claims description 7
- 241000346285 Ostrinia furnacalis Species 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 241000409991 Mythimna separata Species 0.000 claims description 6
- 241000344246 Tetranychus cinnabarinus Species 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 241000607479 Yersinia pestis Species 0.000 claims description 5
- 239000002917 insecticide Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 239000002262 Schiff base Substances 0.000 abstract description 4
- 230000000975 bioactive effect Effects 0.000 abstract description 4
- -1 heterocyclic Schiff base Chemical class 0.000 abstract description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 3
- 150000002611 lead compounds Chemical class 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000000967 suction filtration Methods 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 15
- 239000007788 liquid Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- HPHBOJANXDKUQD-UHFFFAOYSA-N 2-cyanoacetohydrazide Chemical compound NNC(=O)CC#N HPHBOJANXDKUQD-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000012295 chemical reaction liquid Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 125000005909 ethyl alcohol group Chemical group 0.000 description 9
- 239000011259 mixed solution Substances 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 238000001556 precipitation Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000005292 vacuum distillation Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000003026 anti-oxygenic effect Effects 0.000 description 6
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 6
- GFBVUFQNHLUCPX-UHFFFAOYSA-N 5-bromothiophene-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)S1 GFBVUFQNHLUCPX-UHFFFAOYSA-N 0.000 description 5
- 239000003905 agrochemical Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- OUDFNZMQXZILJD-UHFFFAOYSA-N 5-methyl-2-furaldehyde Chemical compound CC1=CC=C(C=O)O1 OUDFNZMQXZILJD-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical class O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/20—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen and oxygen
- C09K15/22—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen and oxygen containing an amide or imide moiety
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/28—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen, oxygen and sulfur
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Materials Engineering (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to heterocyclic Schiff base class compound and application thereof, the heterocyclic radical propylene hydrazide derivative of 2 cyano group of more particularly to N (2 thienyl) methylene 3 and its application.Present invention solves the technical problem that being to provide a kind of heterocyclic Schiff base class compound that can be used as antioxidant and agricultural insecticide, its structural formula is as shown in formula I.The present invention splices principle using bio-active group, heterocyclic compound is introduced into Schiff class compound, some novel structures, the reactive compound of superior activity or active lead compound are found that, so as to establish preferable basis for the initiative of novel antioxidant and insecticide.
Description
Technical field
The present invention relates to heterocyclic Schiff base class compound and application thereof, more particularly to N- (2- thienyls) methylene -2-
Cyano group -3- heterocyclic radical propylene hydrazide derivatives and its application.
Background technology
Antioxidant effectively can delay or suppress many materials, particularly biological big point of sugar, fat, protein, nucleic acid etc.
The oxidation deterioration of son, quite varied application is suffered from many fields：(1) in terms of food processing, antioxidant can suppress
Oxidation of Fat and Oils, prevents it from becoming sour, frequently as food oxydating resistance additive；(2) in life science and medical domain, antioxidant energy
Interior free yl is removed, slows down the formation of peroxidation state, various diseases caused by prevention and treatment free radical improve machine
Body immunocompetence, so as to protect health；(3) in chemical industrial field, antioxidant adds as the stability of chemical products
Plus agent, the antioxygenic property of product is improved, so as to extend its service life.Because antioxidant is in industrial and agricultural production and daily life
Irreplaceable effect is all played in work, therefore, the research and development of the efficient, antioxidant of economy, low toxicity have very
Important meaning.
On the other hand, long-term a large amount of use of agricultural chemicals particularly insecticide not only pollutes environment, destroys the ecological balance,
It also results in serious " 3R " (residual, resistance and pest resurgence) and " three cause " (carcinogenic, teratogenesis shape and mutagenesis) problem.This
A little problems cause the mankind and widely paid close attention to, how to efficiently solve these problems be facing mankind it is one long-term and it is arduous
Task.So, huge challenge is faced with agricultural chemicals, and in the case that the mankind be unable to do without agricultural chemicals, finds high to harmful organism
Effect, to non-target organism safety, degradable in the environment and catabolite to human health and ecological environment security " environment and
Humorous agricultural chemicals " or " environment friendly agricultural " focus into pesticide research and forward position.
Schiff refers to occur condensation reaction and containing for generating by primary amine and aldehydes or ketones>One class of C=N- structures has
Machine compound, both can be isolated from natural products, can also be obtained by artificial synthesized method.Numerous studies table
Bright, Schiff class compound suffers from extremely important in medical science, catalysis, analytical chemistry, corrosion and the field such as photochromic
Effect.Meanwhile, Schiff class compound also has good bioactivity, for example, desinsection, antimycotic, antibacterium, anti-
Cancer, anti parasitic, weeding etc..Therefore, in recent decades, people research and develop to it shows great interest, special
It is not even more of great interest in the field such as biology, medicine, agricultural chemicals, and constantly has structure novelty, excellent performance, work
Come out with unique, the environment-friendly kind of mode.
In recent years, during the research and development of bioactive compound, heterocyclic compound shows more and more important
Effect.Because its selectivity is good, active high, consumption is few, toxicity is low and special in harmful organism biochemical reactions
Property and as research main body.Wherein, the compound such as furans, thiophene, pyridine, pyrimidine, pyrazoles, imidazoles, thiazole, triazole, because not
The disconnected attention for emerging novel agents that some have an epoch-marking significance and causing people, also grinds as bioactive compound
The focus studied carefully and forward position.
Up to the present, it yet there are no what heterocyclic Schiff base class compound was used as antioxidant and agricultural insecticide
Report.
The content of the invention
Present invention solves the technical problem that being to provide a kind of heterocycle that can be used as antioxidant and agricultural insecticide
Schiff class compound.
N- (2- thienyls) methylene -2- cyano group -3- heterocyclic radical propylene hydrazide derivatives of the present invention, its structural formula is such as
Shown in formula I：
Wherein, R1For
R2For hydrogen or halogen；
R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
It is preferred that, R1ForR2For
Hydrogen；R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
It is furthermore preferred that R1ForR2For hydrogen.
It is preferred that, R1ForR2For halogen
Element；R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
It is furthermore preferred that R1ForR2For
Bromine；R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
It is further preferred that R1ForR2For bromine.
The present invention also provides application of the compounds of this invention in antioxidant is prepared.
The compound of the present invention, with excellent antioxygenic property, can be used as antioxidant.
The present invention also provides application of the compounds of this invention in preventing and treating agricultural pests.
The compound of the present invention, it is also possible to make insecticide, to the agricultural evil such as mythimna separata, corn borer, Tetranychus cinnabarinus, Culex pipiens pallens
Worm has preferable cytotoxicity.It is therefore preferable that the agricultural pests are mythimna separata, corn borer, Tetranychus cinnabarinus or Culex pipiens pallens.
The present invention splices principle using bio-active group, and heterocyclic compound is introduced into Schiff class compound, sends out
Some structures novel, the reactive compound of superior activity or active lead compound are showed, so as to be novel antioxidant and kill
Preferable basis has been established in the initiative of worm agent.
Embodiment
The present invention provides compound of the structural formula as shown in formula I：
Wherein, R1For
R2For hydrogen or halogen；
R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
It is preferred that, R1ForR2For hydrogen；
R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.It is furthermore preferred that R1For R2For hydrogen.Further preferably
, R1ForR2For hydrogen.
It is another preferred, R1For
R2For halogen；R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.It is furthermore preferred that R1ForR2For bromine；R3For hydrogen, C1-C4 alkyl
Or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.It is further preferred that R1For R2For bromine.It is furthermore preferred that R1
ForR2For bromine.
The following is currently preferred structural formula.
The compound of the present invention, can be obtained using conventional preparation method.
The compound of the present invention, with excellent antioxygenic property, can be used as antioxidant.
The compound of the present invention, it is also possible to make insecticide, to the agricultural evil such as mythimna separata, corn borer, Tetranychus cinnabarinus, Culex pipiens pallens
Worm has preferable cytotoxicity.
The embodiment of the present invention is further described with reference to embodiment, not therefore by present invention limit
System is among described scope of embodiments.
The synthesis of the compound 1~9 of embodiment 1
Composition principle：
1st, the synthesis of compound 1
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure addition
Funnel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker, with steaming
Distilled water is washed till neutrality repeatedly.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol furfural to be added in 5mL dichloromethane, fully after dissolving, use constant pressure funnel
It is added dropwise in three-necked bottle, reacts 1h, terminal is detected with thin layer silica gel plate (TLC).After reaction completely, reaction solution is poured into
In 500mL beakers, 300mL petroleum ether and stirring is added, there is solid matter precipitation.After its suction filtration and drying, acetonitrile is used：Nothing
Water-ethanol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3423,2207,1685,1612,1557,937；1H NMR(300MHz,
DMSO-d6)δ(ppm):11.77(1H,s),8.66(1H,s),8.16(1H,s),8.07(1H,s),7.68(1H,s),7.48
(1H, s), 7.45 (1H, d, J=2.4Hz), 7.14 (1H, s), 6.84 (1H, d, J=1.5Hz)；13C NMR(75MHz,DMSO-
d6)δ(ppm):158.28(1C),149.40(1C),148.79(1C),144.69(1C),139.00(1C),136.98(1C),
131.98(1C),129.84(1C),128.28(1C),122.70(1C),116.15(1C),114.37(1C),100.00(1C)；
HRMS(ESI)m/z:Calcd for C13H10N3O2S[M+H]+:272.0488,Found:272.0488.
2nd, the synthesis of compound 2
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure addition
Funnel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker, with steaming
Distilled water is washed till neutrality repeatedly.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol 5 methyl furfural to be added in 5mL dichloromethane, fully after dissolving, dripped with constant pressure
Liquid funnel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, reaction solution is fallen
Enter in 500mL beakers, add 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, acetonitrile is used：
Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3441,2208,1672,1604,1543,941；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.67 (1H, s), 8.66 (1H, s), 7.97 (1H, s), 7.70 (1H, d, J=4.4Hz), 7.48 (1H,
D, J=3.2Hz), 7.39 (1H, d, J=3.2Hz), 7.15 (1H, t, J=4.0Hz), 6.53 (1H, d, J=3.6Hz), 2.44
(3H,s)；13C NMR(100MHz,DMSO-d6)δ(ppm):159.89(1C),158.66(1C),147.75(1C),144.56
(1C),139.19(1C),136.70(1C),131.97(1C),129.86(1C),128.37(1C),124.86(1C),116.49
(1C),111.60(1C),97.81(1C),14.35(1C)；HRMS(ESI)m/z:Calcd for C14H12N3O2S[M+H]+:
286.0645,Found:286.0641.
3rd, the synthesis of compound 3
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure addition
Funnel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker, with steaming
Distilled water is washed till neutrality repeatedly.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, by reaction solution
Pour into 500mL beakers, add 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, second is used
Nitrile：Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3433,2207,1682,1581,1551,931；1H NMR(300MHz,
DMSO-d6)δ(ppm):11.79 (1H, s), 8.66 (1H, s), 8.51 (1H, s), 8.13 (1H, d, J=4.2Hz), 7.96 (1H,
s),7.68(1H,s),7.49(1H,s),7.33(1H,s),7.14(1H,s)；13C NMR(75MHz,DMSO-d6)δ(ppm):
158.29(1C),144.92(1C),144.65(1C),138.98(1C),138.84(1C),136.25(1C),135.93(1C),
131.98(1C),129.85(1C),129.02(1C),128.28(1C),116.60(1C),100.79(1C)；HRMS(ESI)m/
z:Calcd for C13H10N3OS2[M+H]+:288.0260,Found:288.0255.
4th, the synthesis of compound 4
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure addition
Funnel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker, with steaming
Distilled water is washed till neutrality repeatedly.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.0.01mol 2- furylacroleins are taken to be added in 5mL dichloromethane, fully after dissolving, with perseverance
Pressure dropping funel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, it will react
Liquid is poured into 500mL beakers, adds 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, use
Acetonitrile：Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3425,2210,1678,1596,1551,926；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.78 (1H, s), 8.65 (1H, s), 8.09 (1H, d, J=12.0Hz), 7.97 (1H, s), 7.71
(1H, d, J=4.4Hz), 7.50 (1H, s), 7.44 (1H, d, J=14.8Hz), 7.16 (1H, s), 7.04-6.94 (2H, m),
6.72(1H,dd,J1=1.6Hz, J2=1.6Hz)；13C NMR(100MHz,DMSO-d6)δ(ppm):158.13(1C),152.46
(1C),151.59(1C),147.36(1C),144.58(1C),139.15(1C),133.84(1C),132.07(1C),129.93
(1C),128.38(1C),120.79(1C),117.54(1C),115.64(1C),113.89(1C),105.55(1C)；HRMS
(ESI)m/z:Calcd for C15H12N3O2S[M+H]+:298.0645,Found:298.0640.
5th, the synthesis of compound 5
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol 5- bromothiophene -2- formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker,
Neutrality is washed till repeatedly with distilled water.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol furfural to be added in 5mL dichloromethane, fully after dissolving, use constant pressure funnel
It is added dropwise in three-necked bottle, reacts 1h, terminal is detected with thin layer silica gel plate (TLC).After reaction completely, reaction solution is poured into
In 500mL beakers, 300mL petroleum ether and stirring is added, there is solid matter precipitation.After its suction filtration and drying, acetonitrile is used：Nothing
Water-ethanol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3432,2215,1687,1616,1554,931；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.86(1H,s),8.58(1H,s),8.19(1H,s),8.08(1H,s),7.47(1H,s),7.36
(1H, s), 7.30 (1H, d, J=2.8Hz), 6.87 (1H, dd, J1=1.6Hz, J2=1.6Hz)；13C NMR(100MHz,
DMSO-d6)δ(ppm):158.44(1C),149.58(1C),148.90(1C),143.95(1C),141.03(1C),137.19
(1C),132.58(1C),131.83(1C),122.86(1C),116.19(1C),115.80(1C),114.50(1C),100.06
(1C)；HRMS(ESI)m/z:Calcd for C13H9BrN3O2S[M+H]+:349.9593,Found:349.9592.
6th, the synthesis of compound 6
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol 5- bromothiophene -2- formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker,
Neutrality is washed till repeatedly with distilled water.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol 5 methyl furfural to be added in 5mL dichloromethane, fully after dissolving, dripped with constant pressure
Liquid funnel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, reaction solution is fallen
Enter in 500mL beakers, add 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, acetonitrile is used：
Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Orange crystal；IR(KBr)νmax(cm-1):3445,2206,1672,1603,1541,971；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.75 (1H, s), 8.57 (1H, s), 7.97 (1H, s), 7.39 (1H, s), 7.34 (1H, d, J=
3.6Hz), 7.28 (1H, d, J=3.2Hz), 6.54 (1H, d, J=3.2Hz), 2.44 (3H, s)；13C NMR(100MHz,DMSO-
d6)δ(ppm):159.95(1C),158.70(1C),147.73(1C),143.65(1C),141.10(1C),136.78(1C),
132.43(1C),131.76(1C),124.94(1C),116.42(1C),115.71(1C),111.62(1C),97.67(1C),
14.36(1C)；HRMS(ESI)m/z:Calcd for C14H11BrN3O2S[M+H]+:363.9750,Found:363.9750.
7th, the synthesis of compound 7
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol 5- bromothiophene -2- formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker,
Neutrality is washed till repeatedly with distilled water.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol thiophene -2-formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, by reaction solution
Pour into 500mL beakers, add 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, second is used
Nitrile：Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Orange powder；IR(KBr)νmax(cm-1):3433,2209,1687,1584,1557,971；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.88 (1H, s), 8.57 (1H, s), 8.51 (1H, s), 8.17 (1H, d, J=4.8Hz), 7.98 (1H,
s),7.37-7.31(3H,m)；13C NMR(100MHz,DMSO-d6)δ(ppm):158.48(1C),145.12(1C),143.89
(1C),141.01(1C),139.01(1C),136.34(1C),136.14(1C),132.58(1C),131.83(1C),129.15
(1C),116.66(1C),115.80(1C),100.84(1C)；HRMS(ESI)m/z:Calcd for C13H9BrN3OS2[M+H
]+:365.9365,Found:365.9365.
8th, the synthesis of compound 8
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol 5- bromothiophene -2- formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker,
Neutrality is washed till repeatedly with distilled water.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.Take 0.01mol 3- pyridine carboxaldehydes to be added in 5mL dichloromethane, fully after dissolving, dripped with constant pressure
Liquid funnel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, reaction solution is fallen
Enter in 500mL beakers, add 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, acetonitrile is used：
Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3445,2230,1663,1614,1551,967；1H NMR(400MHz,
DMSO-d6)δ(ppm):12.07 (1H, s), 9.05 (1H, s), 8.77 (1H, d, J=4.4Hz), 8.59 (1H, s), 8.45 (1H,
D, J=8.0Hz), 8.34 (1H, s), 7.67 (1H, dd, J1=4.8Hz, J2=5.2Hz), 7.41 (1H, d, J=3.6Hz),
7.32 (1H, d, J=3.6Hz)；13C NMR(100MHz,DMSO-d6)δ(ppm):158.09(1C),153.13(1C),151.86
(1C),149.24(1C),144.38(1C),140.81(1C),136.52(1C),132.99(1C),131.93(1C),128.51
(1C),124.68(1C),116.11(1C),116.06(1C),107.97(1C)；HRMS(ESI)m/z:Calcd for
C14H10BrN4OS[M+H]+:360.9753,Found:360.9756.
9th, the synthesis of compound 9
(1) synthesis of intermediate
0.01mol cyano acethydrazide is placed in three-necked bottle, 15mL dichloromethane is added and makees solvent, 3mL acetic acid is urged
Stirred under agent, normal temperature.Take 0.01mol 5- bromothiophene -2- formaldehyde to be added in 5mL dichloromethane, fully after dissolving, use constant pressure
Dropping funel is added dropwise in three-necked bottle, reacts 5h, and terminal is detected with thin layer silica gel plate (TLC).Place reaction liquid into beaker,
Neutrality is washed till repeatedly with distilled water.Divide after liquid and vacuum distillation, suction filtration and dry, obtain intermediate.
(2) synthesis of target compound
Take intermediate 0.01mol to be placed in three-necked bottle, add 15mL absolute ethyl alcohols and make solvent, 3mL triethylamines make catalyst,
Stirred under conditions of 50 DEG C.0.01mol 2- furylacroleins are taken to be added in 5mL dichloromethane, fully after dissolving, with perseverance
Pressure dropping funel is added dropwise in three-necked bottle, reacts 1h, and terminal is detected with thin layer silica gel plate (TLC).After reaction completely, it will react
Liquid is poured into 500mL beakers, adds 300mL petroleum ether and stirring, there is solid matter precipitation.After its suction filtration and drying, use
Acetonitrile：Absolute ethyl alcohol=1：10 mixed solution is recrystallized to crude product, obtains target product.
Yellow powder；IR(KBr)νmax(cm-1):3446,2213,1688,1624,1557,929；1H NMR(400MHz,
DMSO-d6)δ(ppm):11.85 (1H, s), 8.56 (1H, s), 8.09 (1H, d, J=11.6Hz), 7.97 (1H, d, J=
1.2Hz), 7.44 (1H, d, J=14.8Hz), 7.36 (1H, s), 7.30 (1H, d, J=3.2Hz), 7.04-6.93 (2H, m),
6.72(1H,dd,J1=1.6Hz, J2=1.6Hz)；13C NMR(100MHz,DMSO-d6)δ(ppm):152.59(1C),151.59
(1C),147.46(1C),143.69(1C),141.04(1C),134.01(1C),132.61(1C),131.84(1C),120.74
(1C),117.66(1C),115.81(1C),115.60(1C),113.94(1C),105.42(1C),99.99(1C)；HRMS
(ESI)m/z:Calcd for C15H11BrN3O2S[M+H]+:375.9750,Found:375.9753.
The measure of the compounds of this invention insecticidal activity of test example 1
1. for examination insect
The instar larvae of mythimna separata 3, the instar larvae of corn borer 3, Tetranychus cinnabarinus is into mite, the instar larvae of Culex pipiens pallens 3, they be it is indoor often
The sensitive strain that year for many generations raises.
2. the assay method of mythimna separata
Testing sample is dissolved in dimethyl sulfoxide and certain concentration is diluted to the 0.1% Tween-80 aqueous solution, to be not added with
The corresponding solution of testing sample is negative control.Maize leaf is cut into 2 × 4cm segment, taken after soaking 5s in solution to be measured
Open, bottom is put into after draining and is covered with the culture dish of filter paper (6cm), access 15 first 3 instar larvaes, then it is 22 to place it in temperature
~24 DEG C, relative humidity is 60%, and light application time is 14:Continue to raise in 10h laboratory, record death condition after 24h, often
One experiment is repeated 3 times, and calculates corrected mortality with following equation：
3. the assay method of corn borer
Testing sample is dissolved in dimethyl sulfoxide and certain concentration is diluted to the 0.1% Tween-80 aqueous solution, to be not added with
The corresponding solution of testing sample is negative control.The tender fringe of corn and tender bract are cut into segment, taken after soaking 10s in solution to be measured
Open, be put into after draining in a diameter of 6cm, high 9cm glass culture dish, 15 sizes of access are neat, the health age of corn borer 3 children
Worm, then temperature is placed it in for 22~24 DEG C, relative humidity is 60%, and light application time is 14:Continue to raise in 10h laboratory
Support, death condition is recorded after 24h, each experiment is repeated 3 times, and corrected mortality is calculated with following equation：
4. the assay method of Tetranychus cinnabarinus
Testing sample is dissolved in dimethyl sulfoxide and certain concentration is diluted to the 0.1% Tween-80 aqueous solution, to be not added with
The corresponding solution of testing sample is negative control.Gather the big Kidney bean leaf of insect density, carefully choose make health into mite (30~
50) stay on blade face, taken away after the Kidney bean leaf with worm is immersed into solution 5s to be measured, the training that bottom is covered with filter paper is put into after draining
Support in ware (6cm), be placed on temperature for 22~24 DEG C, relative humidity is 60%, and light application time is 14:10h laboratory relaying
It is continuous to raise, death condition is recorded after 24h, each experiment is repeated 3 times, and corrected mortality is calculated with following equation：
5. the assay method of Culex pipiens pallens
Using the method for world health organisation recommendations, testing sample is dissolved in dimethyl sulfoxide and with 0.1% Tween-80 water
Solution is diluted to certain concentration, to be not added with the corresponding solution of testing sample as negative control.Every kind of solution 1mL is taken, is added respectively
Enter into the 118mL wax dixie cups equipped with 99mL distilled water and 20 instar larvaes of Culex pipiens pallens 3, these dixie cups are placed on temperature
For 22~24 DEG C, relative humidity is 60%, and light application time is 14:Continue to raise in 10h laboratory, dead feelings are recorded after 24h
Condition, each experiment is repeated 3 times, and calculates corrected mortality with following equation：
6. result of the test
The desinsection of the compounds of this invention the results are shown in Table 1.
Table 1
a：The average value of three repetitions.
Understand that the compounds of this invention has preferable cytotoxicity to these insects from upper table 1.
The measure of the antioxygenic property of the compounds of this invention of test example 2
1. instrument and reagent
721B type spectrophotometers, 1,1- diphenyl -2- picryls hydrazine (DPPH), 95% ethanol.
2. determination step
(1) preparation of DPPH and sample solution
0.0130 gram of DPPH is accurately weighed with assay balance, is settled to 95% ethanol in 500mL volumetric flasks, obtains concentration
For 26mg/L solution；0.0100g testing samples accurately are weighed, is settled to 95% ethanol in 100mL volumetric flasks, obtains concentration
For 100mg/L sample solution.
(2) 4mL DPPH solution and 1mL95% ethanol solutions is sequentially added in 10mL conical flasks, stable reaction is mixed
Afterwards, using 95% ethanol as reference solution, its absorbance is determined at λ max=518nm, A is designated as0。
(3) 4mL DPPH solution and 1mL solution to be measured is sequentially added in 10mL conical flasks, shakes up, reacts at room temperature
After 40min is stable, using 95% ethanol as reference solution, its absorbance is determined at wavelength X max=518nm, A is designated asS.Often
One experiment in triplicate, and with following equation calculate antioxidant free radical scavenging activity Y (%)：
3. the measurement result of antioxygenic property
Table 2 is when concentration is 100mg/L, clearance rate of the compound to DPPH free radicals
a：The average value of three repetitions.
It was found from upper table 2, the compounds of this invention to the clearance rate of DPPH free radicals all more than 82%, i.e., they have compared with
Good antioxygenic property.
Claims (10)
1. compound of the structural formula as shown in formula I：
Wherein, R1For
R2For hydrogen or halogen；
R3For hydrogen, C1-C4 alkyl or halogen；R4For hydrogen, C1-C4 alkyl or halogen；X is O or S.
2. compound according to claim 1, it is characterised in that：R2For hydrogen.
3. compound according to claim 2, it is characterised in that：R1For
4. compound according to claim 1, it is characterised in that：R2For halogen.
5. compound according to claim 4, it is characterised in that：R2For bromine.
6. compound according to claim 5, it is characterised in that：R1For
7. compound according to claim 1, it is characterised in that its structural formula is as follows：
8. application of the compound described in any one of claim 1~7 in antioxidant is prepared.
9. application of the compound in preventing and treating agricultural pests described in any one of claim 1~7.
10. application of the compound according to claim 9 in preventing and treating agricultural pests, it is characterised in that：The agricultural evil
Worm is mythimna separata, corn borer, Tetranychus cinnabarinus or Culex pipiens pallens.
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| FR2580281B1 (en) * | 1985-04-11 | 1987-09-18 | Synthelabo | NITROFURAN DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
| FR2601368B1 (en) * | 1986-07-08 | 1989-04-07 | Synthelabo | NITROFURAN DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION. |
| DE3768264D1 (en) * | 1987-04-15 | 1991-04-04 | Rohm & Haas | INSECTICIDAL N- (SUBSTITUTED, IF ANY) -N'-SUBSTITUTED-N, N'-DISUBSTITUTED HYDRAZINE. |
| NZ229536A (en) * | 1988-06-15 | 1992-05-26 | Rohm & Haas | N'-substituted-n'-substituted carbonyl-n-substituted carbonyl-hydrazines and pesticidal compositions |
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| CN111004208A (en) * | 2019-12-25 | 2020-04-14 | 西华大学 | 2-cyano-3-thiophene substituted valeramide derivative and application thereof |
| CN111004208B (en) * | 2019-12-25 | 2020-11-24 | 西华大学 | 2-cyano-3-thiophene substituted valeramide derivative and application thereof |
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